The cyclin-dependent kinase 4/6 inhibitor, abemaciclib, exerts dose-dependent cytostatic and cytocidal effects and induces autophagy in multiple myeloma cells

Noriyoshi Iriyama, Hirotsugu Hino, Shota Moriya, Masaki Hiramoto, Yoshihiro Hatta, Masami Takei, Keisuke Miyazawa

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

The D-type cyclin (CCND)-cyclin-dependent kinase 4/6 (CDK4/6) complex has been implicated in multiple myeloma development. We investigated the biological activity of CDK4/6 inhibitor abemaciclib on cell growth and survival in three myeloma cell lines, KMS-12-PE, RPMI 8226, and IM-9. Abemaciclib inhibited myeloma cell growth in a dose-dependent manner in all cell lines, with significant differences seen at a concentration of 320 nM. Treatment with 1 μM abemaciclib increased the fraction of cells in the G0/G1 phase and decreased the fraction in the S-G2/M phases. Further, treatment with abemaciclib at a concentration of 3.2 μM or more showed apparent cytocidal activity accompanied with cytoplasmic vacuolization against myeloma cells. Importantly, abemaciclib induced autophagy in a dose-dependent manner in all three cell lines. These results indicate that the CCND-CDK4/6 complex is closely tied to myeloma cell growth and survival.

Original languageEnglish
Pages (from-to)1439-1450
Number of pages12
JournalLeukemia and Lymphoma
Volume59
Issue number6
DOIs
Publication statusPublished - 3 Jun 2018
Externally publishedYes

Keywords

  • Abemaciclib
  • autophagy
  • cell death
  • multiple myeloma

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